Explorative data analysis of MCL reveals gene expression networks implicated in survival and prognosis supported by explorative CGH analysis
Open Access
- 16 April 2008
- journal article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 8 (1), 1-14
- https://doi.org/10.1186/1471-2407-8-106
Abstract
Background: Mantle cell lymphoma (MCL) is an incurable B cell lymphoma and accounts for 6% of all non-Hodgkin's lymphomas. On the genetic level, MCL is characterized by the hallmark translocation t(11;14) that is present in most cases with few exceptions. Both gene expression and comparative genomic hybridization (CGH) data vary considerably between patients with implications for their prognosis. Methods: We compare patients over and below the median of survival. Exploratory principal component analysis of gene expression data showed that the second principal component correlates well with patient survival. Explorative analysis of CGH data shows the same correlation. Results: On chromosome 7 and 9 specific genes and bands are delineated which improve prognosis prediction independent of the previously described proliferation signature. We identify a compact survival predictor of seven genes for MCL patients. After extensive re-annotation using GEPAT, we established protein networks correlating with prognosis. Well known genes (CDC2, CCND1) and further proliferation markers (WEE1, CDC25, aurora kinases, BUB1, PCNA, E2F1) form a tight interaction network, but also non-proliferative genes (SOCS1, TUBA1B CEBPB) are shown to be associated with prognosis. Furthermore we show that aggressive MCL implicates a gene network shift to higher expressed genes in late cell cycle states and refine the set of non-proliferative genes implicated with bad prognosis in MCL. Conclusion: The results from explorative data analysis of gene expression and CGH data are complementary to each other. Including further tests such as Wilcoxon rank test we point both to proliferative and non-proliferative gene networks implicated in inferior prognosis of MCL and identify suitable markers both in gene expression and CGH data.Keywords
This publication has 70 references indexed in Scilit:
- Genome Expression Pathway Analysis Tool – Analysis and visualization of microarray gene expression data under genomic, proteomic and metabolic contextBMC Bioinformatics, 2007
- Specific Secondary Genetic Alterations in Mantle Cell Lymphoma Provide Prognostic Information Independent of the Gene Expression–Based Proliferation SignatureJournal of Clinical Oncology, 2007
- Cell cycle kinases in cancerCurrent Opinion in Genetics & Development, 2007
- Cell Cycle-controlled Interaction of Nucleolin with the Retinoblastoma Protein and Cancerous Cell TransformationPublished by Elsevier BV ,2006
- The Fos family of transcription factors and their role in tumourigenesisEuropean Journal Of Cancer, 2005
- Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray ExperimentsStatistical Applications in Genetics and Molecular Biology, 2004
- Development of Human Protein Reference Database as an Initial Platform for Approaching Systems Biology in HumansGenome Research, 2003
- Prostaglandin endoperoxide synthase: regulation of enzyme expressionBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1991
- Martingale-based residuals for survival modelsBiometrika, 1990
- Cox's Regression Model for Counting Processes: A Large Sample StudyThe Annals of Statistics, 1982